The clonal expansion of T cells during an infection is tightly regulated to ensure an appropriate immune response against invading pathogens. Although experiments have mapped the trajectory from expansion to contraction, the interplay between mechanisms that control this response is not fully understood. Based on experimental data, we propose a model in which the dynamics of CD4+ T cell expansion is controlled through the interactions between T cells and antigen-presenting cells, where T cell stimulation is proportional to antigen availability, and antigen availability is regulated through downregulation of antigen by T cells. This antigen-dependent-feedback mechanism operates alongside an intrinsic reduction in cell proliferation rate that may also be responsible for slowing expansion. Our model can successfully predict T cell recruitment rates into division, expansion, and clonal burst size per cell when initial precursors are varied or when T cells are introduced late into an ongoing immune response. Importantly, the findings demonstrate that a feedback mechanism between T cells and antigen-presenting cells, along with a reduction in cell proliferation rate, can explain the ability of the immune system to adapt its response to variations in initial conditions or changes that occur later in the response, ensuring a robust yet controlled line of defence against pathogens.

感染期间 T 细胞的克隆扩增受到严格调控，以确保针对入侵病原体的适当免疫反应。尽管实验已经绘制了从扩张到收缩的轨迹，但尚未完全了解控制这种反应的机制之间的相互作用。基于实验数据，我们提出了一个模型，其中通过 T 细胞和抗原呈递细胞之间的相互作用来控制 CD4+ T 细胞扩增的动态，其中 T 细胞刺激与抗原可用性成正比，而抗原可用性通过下调T细胞抗原。这种依赖抗原的反馈机制与细胞增殖率的内在降低一起运作，这也可能是减缓扩张的原因。我们的模型可以成功地预测当初始前体发生变化或当 T 细胞进入持续免疫反应较晚时，每个细胞的分裂、扩增和克隆爆发大小的 T 细胞募集率。重要的是，这些发现表明 T 细胞和抗原呈递细胞之间的反馈机制，以及细胞增殖率的降低，可以解释免疫系统适应初始条件变化或随后发生的变化的能力。应对措施，确保对病原体形成强大而可控的防线。